December 17, 2021
A team of Spanish researchers performed a systematic search of the medical literature and found 28 studies that could be included in a series of meta-analyses of specific measures of sleep impairment. Except for a single meta-analysis with eight studies and 1,713 participants, however, all involved just three to five studies apiece, with anywhere from 121 to just over a thousand participants.
The team examined three sorts of measures:
· Subjective measures, based on self-reporting by ADHD patients.
· Polysomnography is an objective sleep study in which the subject is wired up and studied by technicians in a lab, usually overnight, monitoring multiple body functions, such as brain activity, eye movements, muscle activation, and heart rhythm.
· Actigraphy, a non-invasive objective means of monitoring sleep. The subject wears an actimetry monitor, which is usually worn like a wristwatch on the non-dominant arm. Because it is minimally intrusive, the subject may wear it for a week or more while engaging in normal activities.
In the subjective measures, adults with ADHD generally reported substantially higher sleep impairments than non-ADHD controls. In the largest meta-analysis, covering eight studies and 1,713 participants, adults with ADHD reported moderately longer latency times for falling asleep than controls. In meta-analyses of five studies with between 834 and 1,130 participants, they also reported moderately poorer sleep quality, more frequent night awakenings, being moderately less rested upon awakening in the morning, and moderate-to-strongly greater daytime sleepiness. There was no significant difference in perceived sleep duration.
Polysomnography measures, on the other hand, failed to confirm these subjective impressions. No significant differences were found between adults with ADHD and controls for the initial latency period until onset of sleep, sleep efficiency, waking after the onset of sleep, total sleep time, stage one or stage two sleep, slow-wave sleep, REM (rapid eye movement) sleep, and latency period until REM sleep.
As mentioned above, polysomnography is conducted in lab settings, and therefore inevitably diverges from normal patterns of behavior. Actigraphy helps bridge that gap, by monitoring normal behavior, though with more limited types and precision of data analysis.
And indeed, a meta-analysis of four studies with 222 participants confirmed self-reports that sleep efficiency was moderate to strongly lower in adults with ADHD and that the latency period until the onset of sleep was markedly longer. On the other hand, it found no significant difference in true sleep.
The researchers also looked at prevalence statistics. Whereas the prevalence of sleep-onset insomnia in the general population has been reported in the range of 13 to 15 percent, a meta-analysis of four studies with 466 participants found fully two-thirds of adults with ADHD reporting insomnia, a greater than four-to-one ratio. Similarly, a meta-analysis of three studies with 458 participants found one-third reporting daytime sleepiness, which is twice the rate reported in the general population.
There was no sign of publication bias in any of these results. The authors cautioned, however, about the small number of studies involved, stating this "compromises the generalizability of the findings." Also, some studies included patients undergoing pharmacological treatment for ADHD, "increasing the risk of confounding results."
Moreover, "Sleep onset latency and sleep efficiency were not significantly impaired in the polysomnography, which was incongruent with the actigraphy results. This may be due to a difference in the evaluation context. Whereas polysomnography is considered the gold-standard measure to objectively assess sleep architecture, actigraphy shows a more ecological approach, with the evaluation being conducted in a more naturalistic context for a longer period. However, actigraphy has more environmental influence, which can compromise the data recorded and the interpretation of the results, whereas, in polysomnography, multiple variables can be controlled in the laboratory setting to increase the internal validity of the results. On the contrary, polysomnography studies can produce artifacts due to the unusual circumstances in the setting, so results may need to be interpreted with caution."
The authors concluded, "The results found in the present study show the relevance of addressing sleep concerns in adult populations diagnosed with neurodevelopmental conditions."
Jorge Lugo, Christian Fadeuilhe, Laura Gisbert, Imanol Setiena, Mercedes Delgado, Montserrat Corrales, Vanesa Richarte, Josep Antoni Ramos-Quiroga, "Sleep in adults with autism spectrum disorder and attention-deficit/hyperactivity disorder: A systematic review and meta-analysis," EuropeanNeuropsychopharmacology (2020),https://doi.org/10.1016/j.euroneuro.2020.07.004.
Maternal infections and inflammatory responses during pregnancy have been proposed as risk factors for neurodevelopmental disorders such as ADHD.
Taiwan has a single-payer health insurance system that covers virtually the entirety of its population. Its Ministry of Health and Welfare maintains the National Health Insurance Research Database (NHIRD), with detailed information on outpatient services, hospitalizations, and medical treatment for nearly 99% of all residents.
A Taiwanese study team used NHIRD to examine to examine the relationship between maternal hospitalization for infection, and early childhood infection, and subsequent ADHD in offspring. The study cohort originated with all 3,260,879 individuals born between 2001 and 2018.
The team excluded births from foreign mothers, still births, births with congenital defects, low birth weights, abnormally late births, twins, triplets, and other multiple births, culminating in a final population cohort of 2,885,662 live-born single infants across 1,893,171 families, and 1,864,660 individuals with full siblings from 872,169 families comprising the full sibling cohort.
Study participants were followed until diagnosis of a neurodevelopmental disorder, their death, or the end of 2021.
After adjusting for sex, birth year, paternal and maternal ages, birthweight, birth season, parity, delivery method, 1 minute APGAR score (evaluating baby’s appearance, pulse, grimace, activity and respiration at birth), gestational age, pregnancy and delivery complications, parental history of neurodevelopmental disorders, maternal asthma and diabetes, urbanization level of the residential area, and family’s insurance amount, offspring of mothers hospitalized for infections had 14% greater odds of being subsequently diagnosed with ADHD.
However, in the full sibling cohort of over 1.8 million, this association vanished. That held true for each of the three trimesters of pregnancy. It also held true for bacterial infections. Surprisingly, offspring of mothers hospitalized for viral infections were 24% less likely to be diagnosed with ADHD than their siblings not exposed to maternal viral infection. Because of that, they also had a 6% lower risk overall.
After the same adjustments, early childhood infection was associated with 16% greater odds of being diagnosed with ADHD.
Nevertheless, in the full sibling cohort of over 1.8 million, this association again vanished. That held true overall, as well as separately for childhood infections in months 1-6 and months 7-12. The association vanished altogether both for bacterial infections as well as for viral infections.
The authors concluded, “the results of this nationwide birth cohort study with population and sibling analyses suggest that the association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors.”
Most previous studies of suicide and self-harm risk among persons with ADHD have focused on adolescents and adults. They’ve also tended to be cross-sectional, analyzing data from a population at a specific point in time.
An Australian study team took a different approach, conducting a before-and-after study through the birth cohort of the Longitudinal Study of Australian Children (LSAC), comprising 5,107 children who have been followed up every two years since birth.
The diagnosis of ADHD was based on parents reporting that their child had received a diagnosis of ADHD at or before age ten.
Suicide and self-harm were defined as children’s self-report at age 14 of any thought or attempt of suicide and self-harm respectively over the past year.
The team adjusted for the following confounders: socioeconomic status, birth weight, ADHD medication history, maternal education level, maternal age at birth, experience in bullying victimization at age 12, and depression score based on Short Mood and Feelings Questionnaire (SMFQ).
Of the 5,107 participants, 3,696 had all the valid data required for analysis and were included in the final cohort. Of these, 3.6% were diagnosed with ADHD by age 10.
With diagnosis of ADHD at age 10 and all other factors held constant:
Both depression and exposure to bullying were statistically significant mediators for the relationship. Nevertheless, depression and exposure to bullying each accounted for well under 10% of the overall effect.
Neither socioeconomic status nor maternal factors had any significant mediating effect on outcomes.
Conclusion:
The authors concluded, “This study provides compelling evidence that children diagnosed with ADHD at the age of 10 years face significantly elevated risks of experiencing suicidal thoughts, planning, or attempts, as well as self-harm, by the age of 14 years, which underscores the critical importance of recognizing and addressing these heightened risks in children with ADHD.”
While factors like depression and bullying contribute, ADHD itself remains a key risk factor. Early intervention and strong mental health support are crucial to protecting these children’s well-being.
Noting that “Recent research has demonstrated that some gut bacteria can affect the nervous system,” and speculating that “dysregulation in the gut microbiota may increase the incidence of ADHD by overproducing reactive oxygen and nitrogen species, thereby causing neuroinflammation and oxidative stress”, a Taiwanese study team decided to explore whether early-life use of antibiotics – in the first two years – is associated with increased risk of subsequent diagnosis of ADHD.
Because Taiwan has a single-payer national health insurance system that covers 99.8% of the island’s population, they were able to use the system’s National Health Insurance Research Database (NHIRD) and Maternal and Child Health Database (TMCHD) to include all 1.6 million children born between 2004 and 2012.
Of these, a little over 1.1 million were given antibiotics before turning two years old, and just over 460,000 were not given antibiotics in the same time frame.
The mean follow-up period for records of subsequent ADHD diagnoses was seven years.
The team adjusted for confounding variables: sex, gestational age at birth (weeks), and birth weight (grams) of the children, and age at birth (years), insurance amount (New Taiwan Dollar (TWD)), insurance location, method of delivery, comorbidities, and medication used during pregnancy.
With these adjustments, early-life antibiotics use was associated with a 12% increase in likelihood of being subsequently diagnosed with ADHD.
However, looking at the effects of antibiotics as an undifferentiated grouping turned out to be misleading, because the association was limited to only some classes of antibiotics.
Penicillins were associated with a 22% increase in risk of subsequent ADHD diagnosis, cephalosporins with a 10% increase.
On the other hand, there was absolutely no such association for tetracyclines, macrolides, and quinolones.
The Take-Away:
This study found that children in Taiwan who took certain types of antibiotics before age 2 had a slightly higher risk of developing ADHD later in life. More work is needed to determine if this finding is due to unmeasured confounding before a causal link can be concluded.
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